Overactive bladder is a urological condition defined by a set of symptoms such as urinary frequency, urinary urgency, and urge incontinence. Urinary frequency refers to a condition in which people urinate more than 8 times a day. The urge to urinate may remain even after urination. Urinary urgency refers to a sudden strong urge to urinate with little or no chance to postpone the urination. Urge incontinence refers to an involuntary loss of urine associated with urinary urgency. It is estimated that more than 50 million have overactive bladder globally and it occurs in 22% of people aged 40 or older. Although overactive bladder occurs in both sexes of all ages, it is more frequent in women. It is often associated with frequent contraction of detrusor, the smooth muscle of the bladder. That is, because the bladder muscle contracts more frequently than normal or necessary, the patient feels a sudden, compelling urge to urinate although the bladder is not full. The causes are mostly unknown. In some patients, signaling from the brain to the bladder may be problematic. Damage to the nerves caused by surgical operation or childbirth may also be the cause. Some male patients have the overactive bladder disease along with prostatic hyperplasia.
Overactive bladder significantly affects quality of life by leading to lack of sleep, decreased work efficiency, avoidance of sex, depression and avoidance of inter-personal relations caused by lack of knowledge about the disease and shame. According to a study about the quality of life (SF-36 questionnaire), overactive bladder has a worse effect on quality of life than chronic diseases such as diabetes and hypertension.
Accordingly, development of a novel pharmaceutical compound capable of improving the quality of life of individuals is required.
U.S. Pat. No. 5,382,600 discloses that (substituted) 3,3-diphenylpropylyamine is useful in treating overactive bladder. Especially, the patent teaches that tolterodine, the N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropylamine compound having the formula 2-[(1R)-3-(diisopropylamino)-1-phenylpropyl)]-4-methylphenol is useful.
U.S. Pat. No. 6,517,864 discloses that transdermal administration of tolterodine is effective for treatment of overactive bladder. Particularly, this patent teaches that tolterodine is advantageous for transdermal administration because of high potency and short half-life and a more therapeutic effect on overactive bladder may be attained due to a more constant serum concentration.
Tolterodine is currently marketed as an orally administered drug under the trade name Detrol in the form of tartrate salt. Although a free base form of tolterodine is best suited for transdermal administration, it has decreased stability.